Synergistic effects of antimicrobial peptides and antibiotics against Clostridium difficile.
Antimicrob Agents Chemother. 2014 Jul 14;
Authors: Nuding S, Frasch T, Schaller M, Stange EF, Zabel LT
Accelerating rates of healthcare-associated infections caused by Clostridium difficile with increasing recurrence rates and rising antibiotic resistance have become a serious problem in the recent years. This study was conducted to explore whether the combination of antibiotics with human antimicrobial peptides may lead to an increase of the antibacterial activity. The in vitro activities of the antimicrobial peptides HBD1-3, HNP1, HD5 and LL-37, the antibiotics tigecycline, moxifloxacin, piperacillin/tazobactam or meropenem alone or in combination against 10 toxinogenic and 10 non-toxinogenic C. difficile strains were investigated. Bacterial viability was determined by flow cytometry and toxin production by ELISA. When combined at subinhibitory concentrations antimicrobial peptides and antibiotics generally led to an additive killing effect against toxinogenic and non toxinogenic C. difficile strains. However, LL-37 and HBD3 acted in synergism with all antibiotics tested. Electron microscopy demonstrated membrane pertubation in the bacterial cell wall by HBD3. In 3 out of 10 toxinogenic strains, HBD3 and LL-37, as well as piperacillin/tazobactam or meropenem led to an increased toxin release which could not be prevented by addition of HNP1. Antimicrobial peptides increase the bacterial killing of antibiotics against C. difficile regardless of the mode of action of the antibiotics. Membrane perturbation or pore formation of the bacterial cell wall may enhance the uptake of antibiotics and increase their antibacterial effect. Therefore, the combination of antibiotics with antimicrobial peptides may represent a promising novel approach to treat C. difficile infections.
PMID: 25022581 [PubMed - as supplied by publisher]